摘要:

Variants of B16 melanoma exhibit strikingly different metastatic potential in AY“ (YB16 tumours) and a/a C57BL/6J (MB16 tumours) syngeneic mice. This study focused on relative pigmentation and metastatic potential in eight subline cultures initiated from B16 control and YB16and MB16 tumours. During 6 months ofin vitrogrowth in minimal essential medium, cells displayed a continuous decrease in their ability to form spontaneous lung colonies in 140 syngeneic mice with only persistence of enhanced metastasis-related characteristics depending on genetic change in yellow AY/amice. Conversely, in a parallel experiment in 101 syngeneic micein vitro,cells had a greater capacity to generate experimental metastases; this might be related to successive different environmental factors. In order to compare these prior results obtained in syngeneic mice, the above eight secondary cell lines were inoculated subcutaneously into Swiss nude mice. The primary tumours thus obtained were then serially transplanted monthly during 4 months. The new results obtained in a total of 277 mice showed that metastatic properties of cells were enhanced or restored in nude mice. Various tumour cell environments seem to be responsible for selective pressures that determine the melanoma metastatic potential. New, enhanced, heritable, metastasis-related characteristics can occur in melanoma cells as a result of genetic and metabolic changes and immunologic deficiency of the host. Apparent tumour-host relationship should not be neglected, since it has a clear influence on neoplastic diversity and malignant behaviour.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

CGP 48664A (4-amidinoindan-1-one2‘-amidinohydrazone) is a novel inhibitor of S-adenosyl-methionine decarboxylase (SAMDC), a key enzyme in the biosynthesis of polyamines, which are themselves essential for proliferation of mammalian cells. Seven different human melanoma cell lines were treatedin vitrowith CGP 48664A. High, intermediate and low levels of cytostasis were induced in four, one and two melanoma lines, respectively. This cytostasis was reversed by the addition of exogenous spermidine or spermine to the culture medium. The heterogeneous low metastatic (CGP 48664A-resistant) A375P cells and highly metastatic (CGP 48664A-sensitive) A375SM cells were implanted into the subcutis or injected intravenously into nude mice. Systemic daily administration of CGP 48664A significantly reduced the size of cutaneous lesions and the number of lung metastases in mice implanted with A375SM cells. No beneficial effects were found in mice injected with A375P cells. Drug activity was dose dependent, and maximal effects were observed when treatment began in mice with small tumour burdens. The data suggest that CGP 48664A is effective against melanoma metastasis in nude mice and that its activity should be tested in combination with other cytoreductive agents.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The aim of this study was to assess longitudinally the development of melanocytic naevi in children around the time of their puberty. In Queensland, Australia, 102 schoolchildren born mostly in 1977 or 1978, were examined annually on four occasions from 1990. All naevi on the body except for the scalp and parts covered by a bathing suit were counted by an experienced research nurse or trained assistant according to a set protocol. In addition, each subject's pigmentary characteristics were recorded and height, weight and pubertal status were assessed annually. The findings confirmed that the average number of naevi and average density of naevi (count per m2) on the whole body in boys and girls increase significantly with increasing age and increases were also seen on each of the following anatomic sites: face and neck, back and shoulders, and upper and lower limbs. Children who had a high baseline naevus count, or a large increase in skin surface area during the 3-year follow-up period had the highest absolute increases in naevus count but the smallest proportionate increases. Associations between baseline naevus counts and male sex, light brown or blonde hair, blue or hazel eyes, facial freckling and a tendency to sunburn, which have been previously reported, were also found. However, the independent relations of each of these factors to the increase in new naevi were more complex, once the effects of high naevus counts at baseline and increases in skin surface area were taken into account. No association was found between the incidence of naevi and height, body mass index or time of onset of puberty in this group of adolescent subjects. Beyond personal characteristics, period of birth may also influence the development of naevi, since there has been an apparent increase in naevi in the Australian children in this and other recent studies compared with naevus counts among Australian children of previous generations of comparable age living in similar environments.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

A cross-sectional study was undertaken in 270 inhabitants of The Netherlands (moderate maritime climate, latitude 51°5' N-53°3' N) with skin types Mil and 757 inhabitants of the tropical island Curacao (latitude 12°2' N-12°23' N). The latter group consisted of 282 White individuals (mostly Dutch immigrants) and 475 people with non-White skin types IV, V and VI. All participants underwent total skin examination and melanocytic naevi (MN) and clinically atypical naevi (AN) were noted. There was no statistical difference in the mean number of naevi > 2 mm or > 5 mm between the Curacao and The Netherlands White groups, but the mean number of naevi > 2 mm and > 5 mm was significantly lower in the Curacao non-White group. We found no obvious differences in mean naevus counts between genders and the various comparable age groups. Furthermore, we found no significant difference in mean crude and mean age-standardized prevalence of (one or more) AN between Whites in The Netherlands and on Curacao. The Mantel-Haenszel prevalence ratio weighted for age and gender differences of Curacao Whites vs non-Whites was 5.93 (95% confidence interval 3.9–12.0), demonstrating that AN are significantly less prevalent in darker skin types. In all groups, people with AN had significantly more MN than people without AN. We found a generation-dependent difference in the expression of AN among White inhabitants of The Netherlands and on Curacao, with a higher prevalence of AN in the younger generation.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Combined multi-point linkage analysis in seven Dutch families with FAMMM syndrome confirmed the location of a melanoma susceptibility (MLM) gene in the 9p21 area. The occurrence of a shared high-risk haplotype in six of the families strongly suggests a founder effect in the Leiden region. No indication for locus heterogeneity was observed. Recently, the CDKN2 (p16) gene, an important regulator of the cell cycle, was isolated from the 9p21 region. A 19-bp germline deletion in the CDKN2 gene was detected in the high-risk haplotype, suggesting CDKN2 to be identical to MLM. Loss of heterozygosity studies in melanoma and pancreatic carcinoma from gene carriers strongly support the view that CDKN2 is a general tumour suppressor gene predisposing not only to melanoma but also to other malignancies. Interestingly, the occurrence of apparent clinical FAMMM cases with melanoma but without the high-risk deletion haplotype suggests the necessity of additional (naevus) genes to explain the complete FAMMM phenotype.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

It was recently demonstrated that IL-8 is produced by melanoma cell lines and acts as an essential autocrine growth factor. We studied the constitutive production of IL-8 by melanoma cell lines and the serum concentrations in patients with metastatic melanoma. All of 10 melanoma cell lines investigated constitutively produced IL-8 (mean 315 ± 58 pg/10scells per 24 h. IL-8 was detectable (mean 159 ± 13.1 pg/ml) in the serum of 21 out of 56 patients by an enzyme-linked immunosorbent assay (ELISA; detection limit < 100 pg/ml). There was a significant correlation with tumour load, whereas no correlation with metastatic sites was found. No increased IL-8 levels were seen in healthy controls or patients with metastatic renal cell carcinoma. These results suggest that IL-8 is constitutively produced by melanoma cellsin vivo.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Paraffin-embedded tissue from the primary tumours of 116 patients with malignant melanoma, and in 40 cases also from corresponding metastases, were examined for accumulation ofp53protein. The fraction of tumours with positivep53immunostaining was 13% in the least invasive and 36% in the most invasive primary lesions and 48% in the metastases. Where comparisons could be made, both the level and pattern ofp53immunoreactivity were the same in the primary and metastatic tumours. Nine (50%) patients withp53-positive and 34 (39%) withp53-negative primaries relapsed during the first 5 years, but no difference in disease-free period was observed between the two groups. However, an overall longer survival time was observed among patients withp53-positive primaries, especially for those with tumours less invasive than 3.0 mm. Notably, all 11 patients in this group were alive 5 years after diagnosis of the disease, whereas 15 out of 70 (21%) patients withp53-negative tumours died in same period. The results show that an increased level ofp53protein does not indicate increased degree of malignancy in melanoma, but rather suggests a more favourable disease progression.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The role of elective lymph node dissection (ELND) in primary malignant melanoma is still controversial. Our purpose in this study was to evaluate the benefit from ELND on survival and disease-free survival in malignant melanoma of the trunk and extremities. We performed a matched-pair analysis on 750 patients. There was no significant benefit from wide local excision (WLE) plus ELND compared with WLE in the total group. Increased survival rates were noted for tumour thicknesses of 1.51–4.0 mm for the WLE+ELND group, as shown by 10-year survival rates of 73.1% vs 60.3% (p=0.14). A significant benefit of ELND was detected for malignant melanoma of the trunk (p < 0.05). Disease-free survival rates were significantly higher in the collective treated by additional ELND for all tumour thicknesses (p< 0.05) and even more in intermediate tumour thicknesses of 1.51–4.0 mm (p< 0.001). Our data give further support that ELND may be valuable in improving the prognosis in case of malignant melanoma of intermediate Breslow thickness.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Fotemustine (FM) is a new chloronitrosurea (CNU), chemically characterized by the graft of an aminophosphonic acid on the CNU radical, which makes it highly lipophilic. Following single-institution phase I and II studies with remarkably high response rates of some 40%, including brain metastases of 25% and more, the EORTC-MCG started a multicentre phase II trial to confirm these results according to EORTC guidelines. Treatment consisted of an induction cycle of FM (100 mg/m2on days 1+8+15), followed by maintenance courses (q3w). Fifty-four patients were entered by 11 institutions. General interest in this promising new agent, however, led clinicians of six additional institutions to join the EORTC trial and 90 more patients were included in only 4 months. This rapidly rising accrual rate became inversely related to the physicians' adherence to the eligibility criteria: palliation of symptoms rather than clinical research was the dominant reason to start treatment. Clinical characteristics and results in the eligiblevsnon-eligible patient group (in parentheses) were as follows: male/ female 29/26 (68/65), mean age 54 years (53), ECOG-PS 0–1 (0–4), CR 2 (0), PR 10 (2), NC 17 (5) and for brain metastases: PR 4 (1), NC 2 (1), for an ORR of 12% (5%). Median duration of response was 6 months (range 4–16). The clinically relevant toxicity was limited to the haematopoiesis with delayed platelet nadirs (30% grade III + IV), granulocyte (25% grade III + IV) and the gastrointestinal tract: nausea and vomiting (26% grade II, 18% III, 1% IV). This study confirms that FM is active in melanoma including brain metastases. In an unselected group of patients with increasing tumour load and more advanced disease, the clinically meaningful responses decrease considerably. The responsibility of clinicians for their patients remaining time without symptoms and/or toxicity is stressed.

ISSN:0960-8931    

出版商:OVID    

年代:1995

数据来源: OVID